Unraveling the causal nexus between serum lactate levels and cancer risk: A Mendelian randomization study.

IF 1.4 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL
Lei Yang, Yan Zheng, Faping Li, Jinyu Yu
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引用次数: 0

Abstract

Lactate, traditionally regarded as a metabolic byproduct, has emerged as a potential signaling molecule involved in tumorigenesis. Although numerous observational studies have linked serum lactate levels to various tumors, establishing a direct causal relationship remains challenging. We conducted a 2-sample Mendelian randomization (MR) analysis using genetic instrumental variables to assess the causal effects of serum lactate levels on the risk of various cancer types. The primary analytical method used in this investigation was the random inverse-variance weighted (IVW) method, supported by auxiliary methods such as MR-Egger, weighted median, simple mode, and weighted mode, with the IVW method enabling the meta-analysis of their combined effects. To obtain exposure data, we extracted genome-wide association studies (GWAS) data on metabolite levels from the Canadian Longitudinal Study on Aging and the UK Biobank cohorts. Concurrently, GWAS data for 17 types of cancer were obtained from the IEU Open GWAS project and the GWAS Catalog project. Sensitivity analyses were performed using the Cochran Q test, MR-Egger intercept test, MR-PRESSO, and the leave-one-out method. Our MR analysis identified a causal relationship between serum lactate and endometrial cancer (odds ratio [OR]IVW = 1.1217, 95% confidence interval [CI] = 1.0264-1.2258, P = .0112), melanoma (ORIVW = 1.0015, 95% CI = 1.0006-1.0024, P = .0010), and prostate cancer (ORIVW = 0.9578, 95% CI = 0.9319-0.9844, P = .0020). Notably, elevated lactate levels were identified as a risk factor for endometrial cancer and melanoma, while having a protective effect against prostate cancer. However, this observed relationship was not replicated in other cancer types. Our study, using GWAS data, establishes a causal link between circulating lactate and the risk of endometrial cancer, melanoma, and prostate cancer. The identification of these associations suggests the potential utility of lactate as a biomarker for these cancers or as a target for cancer prevention strategies.

揭示血清乳酸水平与癌症风险之间的因果关系:一项孟德尔随机研究。
乳酸,传统上被认为是一种代谢副产物,已成为参与肿瘤发生的潜在信号分子。尽管许多观察性研究已经将血清乳酸水平与各种肿瘤联系起来,但建立直接的因果关系仍然具有挑战性。我们使用遗传工具变量进行了两样本孟德尔随机化(MR)分析,以评估血清乳酸水平对各种癌症类型风险的因果影响。本研究采用的主要分析方法为随机反方差加权(IVW)法,辅以MR-Egger、加权中位数、简单模式、加权模式等辅助方法,IVW法可对其综合效应进行meta分析。为了获得暴露数据,我们从加拿大衰老纵向研究和英国生物银行队列中提取了代谢物水平的全基因组关联研究(GWAS)数据。同时,从IEU Open GWAS项目和GWAS Catalog项目中获得了17种癌症的GWAS数据。采用Cochran Q检验、MR-Egger截距检验、MR-PRESSO和留一法进行敏感性分析。我们的MR分析发现血清乳酸与子宫内膜癌(比值比[OR]IVW = 1.1217, 95%可信区间[CI] = 1.0264-1.2258, P = 0.0112)、黑色素瘤(ORIVW = 1.0015, 95% CI = 1.0006-1.0024, P = 0.0010)和前列腺癌(ORIVW = 0.9578, 95% CI = 0.9319-0.9844, P = 0.0020)之间存在因果关系。值得注意的是,升高的乳酸水平被确定为子宫内膜癌和黑色素瘤的危险因素,同时对前列腺癌有保护作用。然而,这种观察到的关系并没有在其他类型的癌症中复制。我们的研究使用GWAS数据,建立了循环乳酸与子宫内膜癌、黑色素瘤和前列腺癌风险之间的因果关系。这些关联的鉴定表明乳酸盐作为这些癌症的生物标志物或作为癌症预防策略的靶点的潜在效用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Medicine
Medicine 医学-医学:内科
CiteScore
2.80
自引率
0.00%
发文量
4342
审稿时长
>12 weeks
期刊介绍: Medicine is now a fully open access journal, providing authors with a distinctive new service offering continuous publication of original research across a broad spectrum of medical scientific disciplines and sub-specialties. As an open access title, Medicine will continue to provide authors with an established, trusted platform for the publication of their work. To ensure the ongoing quality of Medicine’s content, the peer-review process will only accept content that is scientifically, technically and ethically sound, and in compliance with standard reporting guidelines.
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